Metabolites of the L-arginine-NO pathway in patients with left-to-right shunt.

OBJECTIVES: The endogenous production of metabolites of the L-arginine-NO pathway has been found to be altered in patients with left-to-right shunt and pulmonary hypertension. The objective of this study was to analyze the influence of age and of the magnitude of the left-to-right shunt on plasma levels of L-arginine, cyclic guanosine monophosphate (cGMP), nitrite and nitrate in children and young adults presenting with left-to-right shunt. METHODS: Twenty-nine patients with ventricular septal defect (n=18), atrial septal defect (n=6) and atrioventricular canal (n=5) were assigned to group I when the ratio of pulmonary to systemic blood flow (Qp/Qs) was less than 1.5 (n=10) and to group II when Qp/Qs > or = 1.5 (n=19). At cardiac catheterization blood samples were taken from the pulmonary vein or left ventricle. In 33 controls peripheral venous blood was obtained. cGMP levels were determined by radioimmunoassay, L-arginine, nitrite and nitrate by high performance liquid chromatography (HPLC). RESULTS: L-arginine plasma levels were lower in group II than in controls (51.7 [23.3-82.2] versus 60.5 [32.4-85.9] pmol/l; p < 0.05 by KRUSKAL-WALLIS). Age did not influence the L-arginine plasma levels (p = 0.30). cGMP levels depended on age (p<0.01) and mean pulmonary artery pressure (p <0.01) but not on high pulmonary blood flow (p=0.85; ANOVA). Plasma nitrite and nitrate were not different in both groups and when compared with controls (nitrite: 26.0 [23.5-31.0] micromol/l; nitrate: 26.8 [24.0-32.0] micromol/l). CONCLUSIONS: Age and pulmonary artery pressure exert important effects on plasma cGMP. Measurement of nitrite and nitrate in plasma alone may not reflect the endogenous NO production. Future studies should evaluate the role of plasma levels of L-arginine in patients with high pulmonary blood flow undergoing repair of their defect.

Unexpected alterations in fentanyl pharmacokinetics in children undergoing cardiac surgery: age related or disease related?

We assessed the pharmacokinetics of fentanyl in 19 infants and children undergoing cardiac surgery for correction of tetralogy of Fallot, A-V-canal and transposition of the great arteries. Distribution T1/2 (10.2 +/- 2.4 min) and total body clearance (13.3 +/- 6.5 ml/kg/min) were similar to adult values. An elimination t1/2 (102 +/- 85 min) shorter than in adults is readily explained by the significantly smaller distribution volume of the drug (1,203 +/- 777 ml/kg). Good correlation was found between distribution volume (Vss) and elimination t1/2 (r = 0.86, p less than 0.01) and between Vss and age of patients with tetralogy of Fallot (r = 0.85, p less than 0.01). However, older children with Fallot's had higher values of PO2 due to a milder condition (r = 0.89, p less than 0.01); consequently PO2 correlated positively with Vss (r = 0.76, p = 0.05). Fentanyl total body clearance (TBC) tends to decrease with age in these patients (r = 0.66, p = 0.05) similar to noncardiac children. Our studies suggest that the alterations in the distribution volume of fentanyl in these children may largely depend upon the severity of the hemodynamic disturbance whereas TBC of the drug may depend on their age.